1, 3-propanediol dicarbamates



United States Patent 3,169,935 1,3-PRQFANED1QL DICARBAMATES George dcStevens, New Providence, N.-.l., assignor to vCilia Corporation,NewYork, N.Y., a corperation of ;.Del'aware No Drawing. Filed Mar. 6, 1962,Ser. No. 177,752 7 Claims. ill. 269-482) This is'a-continuation-in-partapplication of my application Serial No. 110,883, filed May 18, 1961,which in turn is a continuation-in-part application of my applicationSerial No. 55,137, filed September 12, 1960, now abandoned.

The present invention relates to carhamic acid esters,

particularly to compounds of the formula in whichR stands tor acycloaliphatic or acycloaliphaticlower aliphatic radical, R represents alower aliphatic, a cycloaliphaticpa cycloaliphatic-lower aliphatic, a',carbo-, cyclic aryl or a. carbo'c'yclic aryl-lower aliphatic radical,each of the groups Rg and R represents hydrogen, a

lower aliphatic, acarbocyclic aryl or a carbocyclic arylloweraliphaticradicahand each of the groups R and R stands for hydrogen be aloweraliphatic radical. I

A cycloaliph-atic radical R and the cycloaliphatic portion of acycloaliphatic-lower aliphatic radical R represents primarilycycl'oalkyl having from three to eight, especially'from five to six,ring carbon atoms and is represented by cyclopentylior cyclohexyl, as'well a s cyclop ropyl, cyclobutyl, cycloheptyl or cyclo-octyl. Acyclopentylethyl,

re 7 amass Ce Patented Feb. 16, 1965 tertiary butyl, as Well asn-pentyl, isopeiityl, n-hexyl, isohexyl, n-heptyl and the like. A loweraliphatic radical R may also represent lower alkenyl, ag. vinyl, allyl,2- methylallyl, Z-butenyl, B-methyl-Z-butenyl and the like,

or lower alkynyl, e.g. prop-aIg-yl and the like.

a bicyclic carbocyclic aryl, c.g. phenyl, as well as lhaphthyl or2-naphthyl, or carbocyclic aryl-lower alkyl,

especially monocyclic carbocyclic aryllower alkyl, as

. well as bicyclic carbocyclic aryl-lower alkyl, particularly tution.Such substituents are, for example, lower alkyl,

dro'gen, mayalso represent lower aliphatic radicals, espe-i aliphaticradical may also represent a cycloalkenyl radical having from five toeight, preferably from five to six, ring carbon, atoms and stands forl-cyclcpentenyl, Z-cycloheptenyl, 3-cycl ohepten'yl, 2-cyclo-octenyl andthe like. The cyclo'aliphatic radicals may also contain'one ormore thanone substituent, particularly lower alkyl, e.g. methyl,

ethyl and the like, which may be attached, toany of its n'ngcarbonatoms. t

The lower aliphatic portion ofi a cycloaliphatic-lower I 5 v =,t1cularlylower alkyl, e.g methyl, ethyl, n-propyl; 1so aliphatic radical haspreferably from one to three carbon firbpyl. and the like, Oran-y otherlower aliphatic li atoms and may be representedl'by lower alkylehe,eQgJ:

. .40 pentenyl, .3- cyclopentenyl, l-cyclohexenyl, 2-cyclohexen-.

'3lcydOheXeny1 as Wen as Lsycloheptenyl L cyclic' aryl-lower aliphaticradical; these groups have the same meaning as those mentionedhereinabove and 'stahd. primarily for phenyl or phenyl-loweralkyl,"e.g*. benzyl,

methylene, Ll-ethylene, Ll-ethylene, 1-methyl-1,2-eth'- ylene,'Z-methyI-LZ-ethylene,- l,1-propylene, 2,2 propylene or 1,3-propyle1i'e.It mayzalso representlower alkenylene, such as 2propenylene and the likeA cycloaliphatic-lower aliphatic radical R1 may be represented; aboveall, by .cycloalkyl-lower alkyl; e.g.. cyclopropyh methyl,cyclobutylrhe'thyl; cyclopentylmethyl, "l-cyclo 'pentyle'thyl,Z-cyclopnty-lethyl, Z r2 cyclopentyl 2 methylpropyl,3-cyclopentylpropyl, cyclohexylmethyl, 2-cyclo-.

hex'ylethyLi 3-cyclohexylpropyl, cycloheptylmethyl and alke nyl, e.g-3-cyc1opentyl-allyl and the like, or any other suitableeycloaliphatic-lower aliphatic;radical. f

The radical R represents primarily a lower aliphatic radical,especially'lower-alkyl haying from one to 'seven, particularly from oneto four, carbon atoms. A lower the. like, as Well as cycloalkenyl-loweralkyl, e.g. ll-cyclo i pentenylmethyl, 2-(2-cyclopentyl)-ethyl,l-cyclohexenylmethyl, 3 cyclohex enylme'thyl',2-(2-cyclohexenyl).-ethyl,.

Zecycloheptenylmethyl and the like, c ycloalkyl-lower *Dillfil" suitablesubstituents.

than one of the same or of different substitutents, which are attachedto any of the positions available for substieQgfmethyI, ethyl and thelike, lower alkoxy, e.g. methoxy, ethoxy and the like, halogeno, eg.fluoro, chloro,

bromo and the like, trifluoromethyl and the like, or any The' groups Rand R which stand primarily for hy-f ciali-y lower alkyl havingfroirihriei to four carbon atoms, e'lgmethyl, ethyl, n-p'ropyLisopropyl.and thelike, or any other suitable loweraliphatic radical, such as, forex ample, lower alkenyl eg. allyl; 2methylallyl.and' the like, or lower-alkynyl, e.g. propargyl' and the l'ike,'as well as cycloaliphatic'radicals, such as cycloalkyl, e. g.I1cyc lopentyl, cyclohexyl and thelike, radicals- The groups R3 and R may also stand for acarbo'cyclicaryl or a carbo Z-phenylethyl andthe like.

The groups R, and-R which such-as those mentioned hereinbefore. 7

-.- alkl'yl,2-propanediol dicarbani'ates related to'2-is'opropyl- -2'methylLZ-pmpanedioI di'carbarnate meprobamate);

are characterized by pronouneedhiuscie relaxant-prop 1 7 cities whichare acco'nipanied by negligible sedative 'activi- I ties and only slighttranquilizlng effects, i.e. calming'pr'op e'rtiesl which do not impairphysical ability and mental alertness. Contrary to these knowncompounds, the dicarb amates of this invention, \vhenadministeredixiphar macologically effective. doses, exhibit pronouncedtranrelaxantpropertiesh The term tamingiis used-'fto define calmingefiects on naturally lviciousl or artificially 'e'xcited animals; undertheinflu'e'n ce of the compounds o f'this invention, theseanimals losetheir vicious'nessand over-excitedness, while retaining their physicalability *an'd-me ntal alertness.

The compounds of "this represent primarily hydrogen, may also standfor'lower aliphatic radicals,'-par- T invention can, therefo re', ;be .fused 'as' calming and tranquili zingjagents having only moderate, butbeneficial muscle relaxant properties in.

Q) the treatment of hyperactivity (including neuromuscularhyperactivity, resulting, for example, from psychoneurotic conditions orneurological spasticities), aggressiveness and the like.

Particularly pronounced elfects are shown by the compounds of theformula in which the letter In stands for an integer from one to four,the letter It stands for an integer from zero to two, and the letter pstands for an integer from zero to four; the2-cyclopentyl-2-methyl-1,3-propauediol dicarbamate of the formula is acompound of this group with outstanding calming and tranquilizing(taming) etfects, accompanied by moderate muscle relaxant and negligiblesedative properties.

The compounds of this invention, particularly those of the formula inwhich the letters m, n, and p have the previously-given meaning, andespecially the 2-cyclope ntyl-2-methyl-1,3- propanediol dicarbamate, maybe used in the form of pharmaceutical compositions, which contain apharmacologically effective amount of one of the new carbamate compoundsin admixture with pharmaceutical organic or inorganic, solid or liquid.carriers suitable for enteral or parenteral administration. For makingup the preparations there can be employed substances, which do not reactwith the new compounds, such as gelatine, lactose, starches, stearicacid, magnesium stearate, colloidal aluminum magnesium silicate, stearylalcohol, talc, vegetable oils, benzyl alcohols, gums, propylene glycol,polyalkylene glycols or any other known carrier used in medicaments. Thepharmaceutical preparation may be primarily in solid form, for example,as capsules, tablets, dragees acid, e.g. hydrochloric acid (which acidmay be employed in its gaseous form), sulfuric acid and the like. Thereaction is preferably carried out in the presence of an inert solvent,such as, for example, a halogenated hydrocarbon, e.g. chloroform and thelike, an ether, e.g. p-dioxaue, diethyleneglycol dimethylether and thelike, or any other suitable solvent; cooling, and/ or the atmosphere ofan inert gas, e.g. nitrogen and the like, may be required. The metalisocyanate reagents yield N- unsubstituted carbamate compounds.

In the presence of the acid, these metal isocyanates yield cyanic acid,which reacts with the diol starting material to form the desiredcarbarnate. Cyanic acid, a stable compound, may, therefore, also be usedas a reagent in the above conversion of the diols into theirN-unsubstituted carbamates.

The conversion of the hydroxyl into carbamyloxy groups may also beachieved by treating the diol starting material with an organicisocyanate, such as a lower aliphatic isocyanate, for example, loweralkyl isocyanate, e.g. methyl isocyanate, ethyl isocyanate and the like,or any other lower aliphatic isocyanate, as well as a carbocyclicaryl-isocyanate, such as a monocyclic carbocyclic aryl isocyanate, e.g.phenyl isocyanate and the like, or a carbocyclic aryl-lower aliphaticisocyanate, such as a monocyclic carbocyelic aryl-lower alkylisocyanate, e.g. benzyl isocyanate and the like. These reactants, whichare used in the absence or presence of an inert solvent, and may also beformed in the course of the reaction, yield N-substituted carbamatecompounds.

Other reagents, which may also be employed in the conversion of the diolstarting material into the desired dicarbamate product, are, forexample, lower alkyl carbamates, e.g. urethane and the like, whichesters are employed together with a suitable reagent, particularly analuminum lower alkoxide, such as aluminum isopropoxide and the like, inthe presence of an inert solvent, such as a hydrocarbon, e.g. tolueneand the like.

Furthermore, the carbamates may also be formed by reactingthe diol withphosgene and either simultaneously or subsequently with ammonia, aprimary amine or a secondary amine, such as, for example, an N-loweralkylamine, e.g. N-methylamine, N-ethylamine, N-n-propylamine and thelike, an N,N-di-lower alkyl-amine, e.g. N,N-dimethylamine and the like,aniline, an N-lower alkyl-aniline, e.g. N-methyl-aniline,N-ethyl-aniline and the like, an N-phenyl-lower alkyl-amine, e.g.N-benzylamine, N-(2-phenylethyl)-amine and the like, an N-loweralkyl-N-phenyl-lower alkyl-amine, e.g. N-benzyl-N- methyl-amine and thelike; the above reaction is carried out While cooling.

They may also contain, in combination, other pharma in which R; and R5have the previously-given meaning,

the hydroxyl groups into carbamyloxy groups,

The above conversion is carried out, for example, by

treating the diol starting material with a suitable isocyanate reagent.The latter is, for example, a metal isocyanate, particularly an alkalimetal isocyanate, e.g.

sodium isocyanate, potassium isocyanate and the like, or an alkalineearth metal isocyanate, e.g. magnesium isocyanate, calcium isocyanateand the like, or any other suitable isocyanate compound. These reagentsare employed in the presence of an acid, particularly a mineral Thediols used as the starting material and having the formula If: R1-COHaOHCII3OH in which R and R have the previously-given meaning, they beprepared, for example, by converting in a dilower alkyl ot-R -wR-malonate, in which R and R have the previously-given meaning, theesterified carboxyll a rn 3 in which the letter m is an integer from onetofour,

and the letter n -is an .integer fromzero to two, particularly the2-cyclopentyl-2-methyl-1,3-propanediol of the The compounds of thisinvention may also be prepared by converting in .a compound of theformula R2 1 o v I t R -O-CHgr-O- -R H2OCR IOI in whichR and R have thepreviously-given meaning,

and each of the groups R and R" stands for etherified hydroXyl orhalogeno, the groups R. and R" into amino groups. i I A c r V Thesubstituents R and R" in the above di-carbonate starting materials havepreferablythe same meaning and represent primarily etherifiedhydroxyl,'such as lower alkoxy, e.g. methoxy, ethoxy and the like, orany other suitably etherified hydroxyl group, such as CQJIbOCYCllCaryloxy, for example, monocyclic carbocyclic aryloxy, e.g. phenyloxy andthe like, as well as tetrahydropyranyloxy and the like; they mayalso'represent halogeno, e.g.

chloro and the like. The conversion of the groups R and R" into aminogroups is carried out according to known methods, for example, bytreatment with ammonia, a primary amine or a secondary amine; if neces-lsary, such reaction iscarriedout in thepresence'of a f suitable inertsolvent. Cooling or an elevated temperature may be required, and thereaction may be performed in a closed vessel and/ or in the atmosphereofan inert gas, e.g. nitrogen.

The starting materialsused in the above reaction may be formedaccordingto known methods For example,

a 2-R -2-R -l,3-propanediol may be reacted with a clilower alkylcarbonate, e.g. diethyl carbonate and the like,

.to yield a S-RfS-R -l,3-dioxan-2-one; when treated with an alcohol,'for example, a lower alkanol, e.g.methanol, ethanol and the like, thelatter furnishes a 2-R -2-R 1,3-propanediol mono-carbonate (particularlya monolower alkyl-earbonate),.which is then converted into the desired2-R -2.-R -l,3-propanediol di-carbonate; (particularly (ii-loweralkyl-carb'onate) starting material by treat ment with a lower alkylhalogeno-carbonate, e.g. ethyl chlorocarbonate and the like, or anyother analogous reagent, e.g. phenyl -chlorocarbonate and the like. 7The r cyanate in the presence of an acid, e.g. hydrogen chloride and thelike (furnishing cyanic acid as the reagent), as Well as with an organicisocyanate, with a lower alkyl earbamate, or with phosgene and ammonia,a primary amine or a secondary amine, are the preferred methods.

The starting materials used in the above reaction may be preparedaccording to known methods; for example, treatment of apreviously-described 5-R -5-R -l,3-dioxan 2-one with ammonia, a primaryamine or a secondary amine, if necessary, while cooling or at anelevated temperature and/or in a closed vessel, yields the desired 2-R-2-R -1,3-propanediol monocarbamate. The latter may also beobtainedjbyreacting one of the previouslydescribed 2-R -2-R -1,3 propanediol monocarbonates (for example, mono-lower alkyl carbon-ates,monophenyl-carbonates or mono-halogeno-carbonates) with ammonia, aprimary amine or a secondary amine, if necessary, While cooling or at anelevated temperature and/ or in a closed vessel.

The compounds of this invention may also beprepa-red by converting in acompound of the formula V may be required.

' .Thestarting materials used in the above reaction may i "be preparedaccording to -known.methods;.for example,

the hydroxyl group in a 2-R -2-R -L3-propanedio1 monocaroamate may beconverted .into a carbonate ester group by treatment with a carbonicacid diestertsnch as a di-lower ialkylcarbonate, e.g.. diethyl carbonateand V the like), or, more especially, with a halogeno-cai'bonate (suchas a loweralkylchlorocarbonate, e.g. ethyl chloro carbonate and thelike, or any other analogousreagent,

2-R -2-R' -1,3-propanedioll dihalogeno-carbonates (par ticularlydichloro-carbonates), which may also be used as thestarting materials,may be prepared-byqreacting the2-R -2-R 1,3-propanediol with one mol' ofa dihalogeno-carbonate, e.g. phosgene and the like in the presence ofthe necessary amount of a tertiary amine, e.g. N,N-dinrethylanilinefandthe like, to yield a 2-R -2- R -l,3-propanediol mono-halcgeno carbonate(particularly mono-chloro-carbonate), which is then treated withanothermol of a idihalogeno-carbonate, e.g. phosgene and the like, inthe presence of asuitable tertiary amine,.

to yield the desired startinginaterialb The compounds of this inventionmay. also be prepared by converting in a carbamate of the'formula' R OCH O- N in which R R R and R have the previously-given meaning, thehydroxyl g'roup into a earbamyl oxy group.

' The free hydroxyl group of the mono-carbamate start ing material intothe carbarnyloxy groupie carried out I as previouslyfshowmftreatmentwith alkali metal isoe.g. phenyl chlorocarbonateandthe like), as-well asinto a halogeno-carbonate group. by reaction with a,dihalogeno-carbonate (e.g."phosgene and the like) under the-appropriateconditions, if necessary, in the presence of asuitableba sic reagent,while ooolingor at an elevated temperature and/ or in a closed vessel.

The invention also comprises any modification of the 7 process of thisinvention wherein a compound obtainable as an intermediate at any stageof the process is used as the starting material'and the remainingstep(s) of the process is (are) carried out, as Well as any newintermediates; as has been shown in the'conversion of the diol startingmaterial into the dicarbamate compounds,

a monocarbamate intermediate may be formed With isolated; suchcompoundmay then be subjected to further treatment with one of theabove-described reagents.

In the process of this invention such starting materials arepreferablyused which lead to final products Illfill'.

tioned in thejspecifieation as the preferredembodiments of theinvention.

The following examples are intended to illustratethe invention and arenot to be construed'as being limitations thereon. Temperatures are givenin degrees centigradea Erample 1 A solution of 2-cyclopentyl -2.-methyll,3-propanediol in 200 m1, of chloroform is cooled to -5-; 11 g. ofsodium isocyanate is added, and hydrogen chloride gas is bubbled throughthe solution during a period of? two hours.

while maintaining a temperature of O 5L A white .pre:

cipitate is formed; an additional amount of 5 g. of'sodium isocyanate isadded and gaseous hydrogen chloride, is

L passed through the reaction mixture for two more hours. After standingfor one-half hour at the precipitate is filtered off to yield 24 g. of adry, solid material, which is stirred with water and refiltered. Thepure 2-cyclopentyl- 2-methyl-1,3-propanediol dicarbamate of the formulais obtained by recrystallization from a 1: l-mixture of ethanol andwater, M.P. 185-187.

The starting material may-be prepared as follows: To a'solution of 15.1g. of sodium in 225 ml. of ethanol is added 113.4 g. of diethyla-methyl-malonate. The resulting salt is treated with 97.6 g. ofcyclopentyl bromide; the reaction mixture is then refluxed for fourhours. The solvent is removed by distillation, Water is added and theoily layer is extracted with diethyl ether to yield the desired diethyl:x-cyclopentyl-ix-methyl-malonate, which is purified by distillation,B.P. 132136/1213 mm.; yield: 87 g.

A total of 65 g. of diethyl a-cyclopentyl-a-methylmalonate is addeddropwise to a solution of 13.6 g. of lithium aluminum hydride in 300 ml.of diethyl ether. The reaction mixture is refluxed for one hour, cooledand hydrolyzed with water. After stirring for one hour, the solidmaterial is filtered oil, the solvent is removed from the filtrate andhydrochloric acid is added to the residue. The organic material isextracted with diethyl ether, the organic layer is separated andevaporated and the solid material is recrystallized from a mixture ofethanol and water to yield the desired starting material which is usedwithout further purification. The pure 2-cyclopentyl-2-methyl-l,3-propanediol of the formula melts at 9497 after recrystallization froma mixture of ethanol and water.

Example 2 hexyl-Z-methyl-1,3-propanediol dicarbamate of the forwhich ispurified by recrystallization from a mixture of ethanol and water, M.P.148-150.

The starting material may be prepared as follows: A-

solution of 3.8 g. of diethyl a-cyclohexyl-a-methyl-malomate in 30 ml.of diethyl ether is added dropwise over a period of 1% hours to avsuspension of 1.15 g. of lithium aluminum hydride in 50 ml. of diethylether while maintaining refluxing conditions. cooled, and 6.6 ml. ofwater is added while stirring to decompose the complex. After standingovernight, the solid material is'filtered 01f, the filtrate isevaporated, and the residue is taken up in hydrochloric acid. Theorganic material is extracted with diethyl ether, the organic solutionis dried over magnesium sulfate and is evaporated to The reactionmixture is F! a yield the 2-cyclohexyl-2-methyl-1,3-propanediol of theformula CHr-OH CH3 CHCCHz-OH CHFCHZ CHz-OH which melts at Example 3 To acold solution of 2.5 g. of 2-cycloheptyl-2-methyl-1, 3-propanediol inml. of chloroform is added 2.5 g. of sodium isoeyanate; the reactionmixture is treated with dry gaseous hydrogen chloride for two hours andan additional amount of 1.1 g. of sodium isoeyanate is added. Aftertreatment with gaseous hydrogen chloride for an additional hour, thedesired Z-cycloheptyl-Z-methyl-1,3propanediol dicarbamate of the formulaCH3CH2 CH3 H10 5 CH- -crIi0H 11,0

Hg-OH GET-CH, I M.P. 60, is obtained according to the procedure inExample 2.

Example 4 A solution of 4.2 g. of 2-cyclopentylmethyl-Z-methyl-1,3-propanediol in chloroform is treated with 4.23 g. of sodiumisocyanatc; hydrogen chloride gas is bubbled through the solution, anadditional 2.12 g. of sodium isoeyanate is added and treatment withhydrogen chloride gas is continued for an additional two hours. Thereaction mixture is worked up as described in Example 2 to the desired2- cyclopentylmethyl-Z-methyl-1,3-propanediol dicarbamate of the formulawhich melts at 119121 after recrystallization from a mixture of ethanoland water.

The starting material may be prepared by adding a solution of 6.6 g. ofdiethyl ix-cyclopentylmethyl-a-methylmalonate, B.P. 146-148/ 12 mm., in30 ml. of diethyl ether to a refluxing suspension of 1.95 g. of lithiumaluminum hydride in 50 m1. of diethyl ether; the resulting complex isdecomposed by adding 11.2 ml. of water, and the desired2-cyclopentylmethyI-Z-methyl-1,3-propanediol of the formula is obtainedaccording to the procedure described in Exam ple 2; the impure materialmelts at, 7078.

- HgC-CH3 if H20 Hz 7 H C-CH, o

The starting material may be prepared as follows: A total of 22.8 g. ofdiethyl u-cyclopentyl-malonate, B.P.

133'134/12mm., is addedtoa suspension of 4.6 g. of

a 52 percent sodium hydride suspension in mineral oil;

the reaction takes place aftershortly heating the mixture, and iscompleted after refluxing for 1- /2 hours. 4.9 'g.

' of cyclopentyl bromide 'is slowly added; and the reaction mixture isrefluxed overnight. The precipitate is added to the residue andtreatedwith'a minimum amount of water to dissolvethe inorganic material,Theorganic layer is separated, the aqueous phase isextracted withdiethyl ether, and the extract is cornbined with the separated organicmaterial. The diethyl ether solution is dried over i magnesium sulfate,filtered and evaporatedand the diethyl which melts at 95-100 which ispurified by distillation, B.'P. .120/0.1 mm. The starting material isprepared as follows; A solution of 32.0 g; of2-cyclopentyl-2-rnethyl-*1,3-propanediol in .500 ml. of toluene and 24.2g. of N,N dirnethylaniline is cooled to 5 and 20.0 g. of phosgene in 140ml. of toluene is added slowly. The reaction mixture is stirred at roomtemperature for three hours, then extracted with 5 percent aqueoushydrochloric acid and dried over magnesium sulfate. After filtration,the organic solution (containing 3-chlorocarbonyloxy-2-cyclopentyl-2-methyl-propanol) concentrated underreduced pressure and the residue is treated with 1000 ml, ofconcentrated ammonium hydroxide for 24 hours. The organic material isextracted with ethyl acetate, and the organic solution is driedover'magnesiumsulfate, filtered and evaporated. The residueis extractedwith diethyl ether; the 'first crop of crystalline material representsthe 2-cyclopenty1-2-methyl-1,3-propanedi0l di-' 'carbamate, which isfiltered 01f. The filtrate is allowed to stand for three days and yieldsthe 3-carbamyloxy-2- cyclopentyl-Z-methyhpropanol of the formula afterrecrystallization from ethanol. i

Other compounds prepared according to one of the previously-describedprocedures are, for example,

a,e-di-cyclopentyl-malonate is distilled, B.P. 152-168/ '12 l A solutionof 2.4 g. of the diethyl a,er-di-cyclopentyl malonatein 20 m1. ofdiethylether is added to; a suspension of 0.62 g. of lithium aluminumrhydridein diethyl ether; the reaction mixture isrefl'uxedfor onehour andallowed to stand overnight. The complex is decomposed by adding 3.6 ml.of water; dilute aqueous hydrochloric acid is added to complete thesolution. The organic layer is separated, the aqueous phase is extractedwith diethyl I ether, and the combineddiethyl ether extracts are dried,filtered and"evapor'ated1to yieldthe desired 2 2 di-cyclo--pentyl-1,3-propanediol of the. formula a Example6 To a solution of 3.0g.of 3-carbamyloxy-2-cyclopentyl- Z-methyl-propanol in 150 mLof tolueneis added 1.32 ml. of pyridine; the mixture is cooled to 5 and treatedwith 1.66 g. of phosgene in1'6 ml. of toluene, while maintaining2-cyclopropyl 2-methyl-1,3 -propanediol dicarbamate,2-cyclobutyl-2-methyl 1,3-propanediol dicarb'amate,2-cyclopentyl-2-ethyl-1,3:propariediol dicarbarnate,

- 2-.cyclopentyl-2-n-proply-1,3-propanediol dicarbamate,

f 2-cyclopentyl-2-isop'ropyl-1,3-propanediol-dicarbarnate,

Z-cyClope'rityl-Z-isobutyl-1,3-propanediol dicarbamate,1-carbamyloxy-Z-cyclohexyl-2-n1ethyl-3 (N-methylcarbamyloxy)-propane, i2-'cyclopentyl -2-methyl-1,3 -di- (N methyl-carb amyloxy propane. 1

Z-cyclohexylZ-ethyl-l,3-propanediol dicarbamate,

. 2-cyclohexyl-2-n-propyl-1;3-propanediol dicarbamate," 2-cyclohexyl 2isopropyl-1,3-propanediol dicarbarnate,2-n-butyl-2-c'yclohexyl-1,3-propanediol dicarbamate,

. '50 i as a thick oil, which is used without further purification.

the temperature of below 5. The reaction mixture is i stirred for threehours at room temperature; the pyridine hydrochloride is filtered off,and the filtrate is washedi The compounds of this invention maybe used.in the,

with 5' percent aqueous hydrochloric acid. The organic solution(containing the 1-carbamoyloxy-3chlorocarbonyloxy-2-cyc1opentyl-2-methyl propane) is dried over mag-'nesium sulfate, filtered and then treated'with gaseous N- methyl'aminc.The N-methylamine hydrochloride is fil- 'tered off; the filtrate isdried over magnesium sulfate and 1 evaporated to yield the1-carbamyloxy-Z-cyclopentyl-Z- methyl-3-(N-methyl-carbamoyloxy)-propaneof the formula Ingredients:

2 cyclohieptyl-Z-n-propyl-1,3-propanedi0l dicarbamate;:2-cyclopentylmethyl-2-ethyl-1,3-propanediol v dicarbamate,

2rcyclopentyhnethyl-2 n propyh 1 3 -pro p ane diol diearbarnate,

2- l-cyclopentylethyl) -2-methyl-1,3-propanediol dicarbamate,

2-cyclohexylmethyl-2-methyl-1,3-propanediol dicarbamate,

'2-(Lcyclbhexylethyl)-2-methyl-1,3 propanediol dicarbarnate, r V2-(l-cyclohexylethyl)-2-methy1 1,3-pr0panediol -dica'rbamate, V2-(2-cyc1ohexylethyl) -2-n-propyl-l,3-propanediol dicarbamate and thelike. 1

Example 7 form of'pharmaceutically acceptable'compositions.' Thus,

tablets containing 0.5 g. of 2-cyclopentyl-2-n1ethyl-1,3! propanediol.dicarbamate asthe active ingredient may be prepared as follows (for120,000 tablets) G. 2-cyclopentyl-2-methyl-1,3-propanediol dicarbamate"60,000 Colloidal aluminum magnesium, silicate of" high viscosity 1,500Corn starch Talcum 1,,87-5

"l l r The 2-cyclopentyl-2-methyl-1,3-propanediol dicarbamate, thealuminum magnesium silicate and 1,750 g. of corn starch are mixed atslow speed for twenty minutes. 5,260 g. of corn starch is suspended in6,000 m1. of water and stirred until a uniform suspension is obtained. Atotal of 18,000 ml. of boiling water is added to the suspension andstirring is continued until a smooth paste is formed. The latter isadded to the first mix and agitation is continued until granules areformed. The wet mass is passed through a No. stainless steel screenemploying a mill operating at low speeds. The screened material is driedat 110 until the moisture content is between 2 and 3 percent; the massis passed through a No. wire mesh screen again employing a mill, thistime at medium speed. The ground granules are placed in a mixer, thetalcum, the stearic acid and the remaining corn starch are added; themixture is mixed well and the granules are compressed into tabletsweighing 0.625 g. using a compressing machine equipped with inchstandard concave punches (uppers bisected and lowers monogrammed) andinch dies.

What is claimed is: I 1. A compound of the formul having from three toeight carbon atoms, and each of 1 12 the groups R and R is a memberselected from the group consisting of hydrogen and lower alkyl.

2. A compound of the formula References Cited by the Examiner UNITEDSTATES PATENTS 2,555,912 6/51 Arnold 260617 2,837,560 6/58 Beinfest.2,884,444 4/59 Berger. 7 2,917,549 12/59 Has'ek et a1. 260617 2,921,9661/60 Carbon et al. v 260617 2,934,559 4/ Beinfest et a1 260482 2,937,1195/60 Berger.

2,971,979 2/61 Meiser et a1. 260482 LORRAINE A. WEINBERGER, ActingPrimary Examiner.

LEON ZITZER, DANIEL D. HORWlTZ, Examiners.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No 3,169,985 February 16, 1965 George de Stevens ove numbered patpears in the abread as certified that error ap d Letters Patent should It is hereby dthat the sai ent requiring correction an corrected below.

lines 29 to 34, the formula should appear as Column 3,

d of as in the patent:

shown below instea CH (c s H ,CH- (c n c line 57, for "with" read andcolumn 6,

14th day of September 1965.

Signed and sealed this I (SEAL) 1 Attest:

ERNEST W. SWIDER EDWARD Jo BRENNER Attesting Officer Commissioner ofPaten

1. A COMPOUND OF THE FORMULA